Enhanced wild-type p53 expression by small activating RNA dsP53-285 induces cell cycle arrest and apoptosis in

Dengqiang Lin1, Li Meng1, Feifei Xu1

  • 1Department of Urology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, P.R. China.

Oncology Reports
|October 20, 2017
PubMed

Insights

Upregulating wild-type TP53 shows anti-tumor effects in pheochromocytoma (PHEO) models. This approach, using RNA activation, successfully inhibited PHEO cell growth and induced apoptosis, offering a potential new therapy for this rare cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Malignant pheochromocytoma (PHEO) often presents with metastasis, limiting traditional chemotherapy efficacy.
  • TP53 mutations are observed in PHEO, suggesting a role in disease progression.
  • The therapeutic potential of wild-type TP53 upregulation in PHEO is unexplored.

Purpose of the Study:

  • To investigate the antitumoral effects of wild-type TP53 upregulation in PHEO.
  • To explore RNA activation as a method to increase wild-type TP53 expression in PHEO cells.

Main Methods:

  • Utilized RNA activation (RNAa) by transfecting synthetic dsP53‑285 into the PC12 PHEO cell line.
  • Assessed cell cycle progression (G0/G1 to S phase transition) and apoptosis induction.
  • Validated findings in vivo and examined reversibility using siRNA targeting p53 mRNA.

Main Results:

  • Upregulation of wild-type p53 via RNAa inhibited PC12 cell proliferation by blocking G0/G1 to S phase transition.
  • Induced apoptosis in PHEO cells.
  • Demonstrated that these antitumoral effects were reversible upon p53 knockdown.

Conclusions:

  • Wild-type TP53 upregulation exhibits significant antitumoral effects in PHEO models.
  • RNA activation of TP53 presents a potential therapeutic strategy for malignant pheochromocytoma.
  • Further research into TP53 and other anti-oncogenes could yield novel treatments for PHEO.

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